Autologous bone marrow transplantation for childhood acute lymphoblastic leukemia: a novel combined approach consisting of ex vivo marrow purging, modulation of multi-drug resistance, induction of autograft vs leukemia effect, and post-transplant immuno- and chemotherapy (PTIC)

Abstract

Summary:In an attempt to reduce the high relapse rate associated with ABMT, five children with high-risk first CR and 19 in second or subsequent CR lacking matched family allogeneic donors underwent ABMT with chemopurged bone marrow utilizing verapamil (VPL), vincristine, and VP-16. Patients were conditioned with TBI, VPL bolus and infusion with VP-16 and cyclophosphamide. The first cohort of patients (n = 4) received only cyclosporin A (CsA). The second cohort (n = 7) received CsA and alpha interferon (total = 11 with post-transplant immunotherapy alone.) The third cohort (n = 13) received CsA and six alternating cycles of ␣IFN and chemotherapy and six additional cycles of chemotherapy (vincristine, VP-16, Ara-C, prednisone) followed by G-CSF (post-transplant immune chemotherapy (PTIC)). The 2-year DFS is 42 ؎ 10% (90% confidence interval (CI) is 26.5-58.5%) and 2-year overall survival is 54 ؎ 10% (90% CI is 37.5-70.5%). Furthermore, patients receiving PTIC (n = 13) vs immunotherapy alone (CsA ؎ ␣IFN) (n = 11) had a substantially better 2 year DFS and OS: 69 ؎ 13% vs 13 ؎ 12% and 85 ؎ 10% vs 25 ؎ 15% (P = 0.008 and P = 0.06, respectively). These results suggest that the use of ABMT with chemopurging, combined with PTIC is well tolerated and may be an alternative new approach in the treatment of a subset of children with high-risk first CR or у second CR ALL who lack closely matched family-related allogeneic donors. Bone Marrow Transplantation (2001) 27, 145-153.

Criteria for and outcomes of allogeneic haematopoietic stem cell transplant in children, adolescents and young adults with acute lymphoblastic leukaemia in first complete remission

“…There is evidence of a significant graft‐versus‐leukaemia (GVL) effect that justifies the use of matched family or alternative donor stem cell transplant in patients thought to be at high risk of relapse. In addition, there has also been some data to suggest that in patients who lack a suitable allogeneic donor, autologous stem cell transplant with chemo‐purged bone marrow and post‐transplant immunochemotherapy is safe and can induce a GVL effect leading to prolonged DFS (Houtenbos et al , ). A recent review of over 1000 patients aged 0–18 years old among 14 cooperative groups during a 15 year period identified many of the high risk features of ALL already discussed previously in this article.…”

Combined chemotherapy and ALA-based photodynamic therapy in leukemic murine cells

“…Bone marrow purging consists in treating in vitro the marrow autograft in an attempt to decrease or eliminate leukemia cells. This can be performed using chemotherapeutic agents such as 4-hydroxi cyclophosfamide (4-HC) or maphosfamide (ASTA-Z), immunologic techniques, long-term culture, or physical methods [6].…”

Immature CD34+CD19− progenitor/stem cells in TEL/AML1-positive acute lymphoblastic leukemia are genetically and functionally normal

“…Transplantation protocols often include purging of the autologous stem cell products to minimize the potential risk of reinfusing leukemic cells. 33,34 However, purging strategies based on the expression of lymphoid markers will only be effective if all leukemic cells, including putative immature ALL stem cells, express the respective marker.…”